The overall purpose of this program is a multidisciplinary basic and clinical investigation of the structural, contractile and biochemical adaptations of skeletal and cardiac muscle to maturation, neural control, exercise and various neuromuscular disorders with the objective of characterizing those pathophysiologic events most likely to result in abnormal muscle structure and function. The ultimate goal is the elucidation of mechanisms basic to muscle disease and to identify methods for alleviating, treating or preventing these disorders. The 18 studies in the program represent a spectrum of interrelated investigations carried out in a horizontal plane at several biological levels; along a vertical plane, the spectrum includes multiple interspecies comparisons. Both the basic and clinical research studies are focused on a range of problems relevant to related diseases (myopathies) and disciplines (muscle biology). Study objectives include: (1) histological, cytochemical, and biochemical investigations of normal and myopathic skeletal and cardiac muscle in animal models, (2) the mode of regulation of muscle by neural activity and the contractile characteristics of normal and myopathic muscles in animal models and (3) a comparative study of the structural, contractile and metabolic responses of skeletal and cardiac muscle to diabetes, infections, exercise and congenital disorders of muscle in humans.